Zoila Areli Lopez Bujanda
Despite the profound and durable clinical responses to checkpoint therapy that have led to FDA approval for PD1 and CTLA4 blockade in several tumor types, patients with prostate cancer have yet to benefit from these therapies. Understanding the immunosuppressive pathways underpinning the lack of anti-tumor responses in prostate cancer, as well as the mechanisms that regulate these pathways, may lead to novel treatment paradigms that unleash the potential of checkpoint therapy in the treatment of prostate cancer.
As a Ph.D. student in Charles Drake’s laboratory, I found that an important immune-resistance mechanism is initiated as a byproduct of the main line of treatment for prostate cancer, androgen deprivation therapy (ADT). Androgen receptor loss of signaling following ADT induces prostate tumor cells to upregulate the expression of IL-8. IL-8 is a chemokine that recruits suppressive neutrophils in the context of cancer known as polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs). Inhibiting IL-8 signaling led to a reduced recruitment of PMN-MDSCs to prostate tumors. Furthermore, hindering the recruitment of PMN-MDSCs in combination with checkpoint blockade significantly delayed tumor outgrowth. Our data provide a rationale for targeting PMN-MDSC recruitment in combination with immune checkpoint blockade for the treatment of prostate cancer before ADT is administrated, when the immune-suppressive microenvironment has not been yet established. Based on these findings, our group has launched an investigator-initiated clinical trial to evaluate targeting PMN-MDSCs in combination with checkpoint blockade before ADT in prostate cancer patients.
Questions & Answers
Why did you choose Johns Hopkins for your work?
I was fortunate to come to Johns Hopkins for a short internship while I was pursuing my master’s degree in Mexico, and I can honestly say that I fell in love with the place. I was impressed by the level of collaboration between laboratories and the commitment of its people to work together to achieve great things. My interest in translational research was the driving force that led me to choose the pathobiology program for my Ph.D. studies.
What does receiving this award mean to you personally and professionally? Do you have any connection with the particular award you received?
This award provides a validation of my scientific achievements to date. It is also a motivator for me toward continuing down the path of a career researcher.
What contributed to your project’s success?
Definitely, my Ph.D. adviser, Charles G. Drake (Chuck), has been a source of inspiration all along the way. Having a mentor who trusted me to work independently, while being approachable and critical with my research was very important to my project’s success. I would also say that working among scientists with varied expertise and a desire to collaborate has also been instrumental for the success of this project.
What thoughts do you have about Young Investigators’ Day itself, as a celebration of the roles students and fellows play in research at Johns Hopkins?
These awards highlight the importance of the contributions of scientists in training and provide a platform for them to network and build potential future collaborations.
What has been your best/most memorable experience while at Johns Hopkins?
One of my most memorable moments at Johns Hopkins happened while working on my first doctoral project. I discovered a myeloid gene signature contained in a data set that was isolated on a fluorescent tag reporter that was only expressed in prostate tumor cells. This finding was a steppingstone for the project that eventually lead me to receive The Mette Strand Research Award and initiated a new area of research in the laboratory.
Tell us something interesting about yourself.
I am a product of public investments in education. Scholarships have been a cornerstone of my education since middle school. Through public funds, I was fortunate enough to experience research internships in Spain and the U.S., and from these experiences, I was exposed to female role models in science who inspired me to be where I am today. In the future, I want to offer the same guidance I had to up-and-coming scientists who need it.
As a Ph.D. student, I have become interested in furthering opportunities for underrepresented minorities in the sciences. I served as the treasurer for a graduate student organization that is focused on fostering minority students in science. As a researcher, I am highly interested in training future scientists from underrepresented communities.